The present Program Project brings together established investigators from many different disciplines to study the "Neurobiology of Environmental Pollutants." A multifaceted, but well integrated, interdisciplinary approach will be used to study a variety of potentially toxic compounds, with lead being focussed on at the outset as a prototype problem. Among other compounds to be studied are: (1) heavy metals besides lead, (2) organophosphate anticholinesterase compounds used as pesticides, (3) noxious gases such as carbon monoxide, (4) steroid hormones, hormone analogs and blocking agents used in birth control regimens and/or to stimulate rapid growth of livestock for meat production and (5) additional compounds that come to be of concern to governmental agencies as potential toxins. Using well-defined animal models in terms of closely controlled exposures to various doses of toxins and precise determinations of actual body burdens of toxins produced, a variety of dependent variables relevant to central nervous system (CNS) functions will be assessed. This includes a heavy emphasis on screening for behavioral changes in (1) locomotor activity levels and habituation processes, (2) consumption behaviors relevant to nutritional state, (3) sex and maternal behavior, (4) emotionality and aggressiveness, and especially (5) learning and memory processes as assessed by operant conditioning paradigms. Attempts will be made to relate behavioral changes to morphological, biochemical and physiological effects induced by toxins. These will include effects on (1) CNS neurotransmitter systems, (2) neuroendocrine mechanisms and (3) CNS protein synthesis mechanisms (myelination). Also, mechanisms determining cerebral flux of toxins into the brain and the distributions of toxins in brain and endocrine organs will be studied. Neuropharmacological research will screen various drugs for use as therapeutic agents to ameliorate toxin effects and as diagnostic screening tools for detecting specific neuropathological damage patterns. Clinical epidemiological surveys of retarded children populations will be done to assess past toxin exposures.